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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

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Autophagy inhibition and mitochondrial remodeling join forces to amplify apoptosis in activation-induced cell death

Mauro Corrado1,2, Silvia Campello2,3

  • 1a Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine , Padova , Italy.

Autophagy
|September 16, 2016
PubMed

Insights

Activation-induced cell death (AICD) inhibits autophagy early, causing mitochondrial fragmentation and apoptosis. Bulk autophagy clears dysfunctional mitochondria, suggesting new immune modulation strategies.

Area of Science:

  • Immunology
  • Cell Biology
  • Mitochondrial Dynamics

Background:

  • Autophagy and mitochondrial dynamics are crucial under stress.
  • Their interplay during physiological cell death, like activation-induced cell death (AICD), remains poorly understood.
  • Understanding this crosstalk is vital for immune regulation.

Purpose of the Study:

  • To investigate the relationship between autophagy and mitochondrial changes during AICD.
  • To determine the specific roles of macroautophagy and mitophagy in AICD.
  • To explore potential therapeutic targets for immune modulation.

Main Methods:

  • Studied T-cell receptor (TCR)-dependent AICD.
  • Analyzed mitochondrial structure and function (fragmentation, depolarization).
  • Assessed autophagy and mitophagy inhibition/activity during AICD.

Main Results:

  • Autophagy is inhibited early during AICD.
  • Mitochondrial fragmentation and cristae remodeling accompany autophagy inhibition.
  • Bulk autophagy, not just mitophagy, removes dysfunctional mitochondria during AICD.

Conclusions:

  • AICD involves early autophagy inhibition and mitochondrial restructuring to promote apoptosis.
  • Autophagy plays a key role in clearing damaged mitochondria during AICD.
  • These findings offer novel strategies for modulating immune function in autoimmunity and immunotherapy.
Keywords:
AICDT cellsapoptosisautophagymitochondriamitochondrial dynamics

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